Asthma is a chronic respiratory disease which is susceptible to children and causes great harm to them. Recently, Interferon-related developmental regulator 1 (IFRD1) was proved to be participant in regulating lung diseases, and its abnormal expression was shown in pathological airway tissues. Our study aimed to demonstrate the role and modulatory mechanism of IFRD1 in the pathogenesis of asthma. First, we evaluated the expression of IFRD1 in the lungs of asthmatic patients. C57BL/6 mice and human bronchial epithelioid (HBE) cells were respectively induced by ovalbumin (OVA) and lipopolysaccharide (LPS) to construct asthma models in vivo and in vitro. Using adenovirus and pcDNA vectors, we carried out overexpression assays on mice and cell models. Additionally, the potential mechanism of IFRD1 on regulating asthma process was elucidated by targeting NF-κB pathway. The results showed that IFRD1 was significantly down-regulated in asthma lung tissues, as well as the in vivo and in vitro models of asthma. Besides, OVA induced the inflammation responses and hyperreactivity of airway in mice, and LPS also caused inflammatory cytokine secretion and apoptosis of HBE cells, while cell viability was inhibited. However, IFRD1 overexpression dramatically reversed the effects of OVA and LPS. We subsequently discovered that the NF-κB pathway was activated in asthmatic cells, and NF-κB signaling activation was involved in IFRD1 regulated asthma responses of HBE cells. In conclusion, our study indicated that IFRD1 inhibited the asthmatic responses of airway via the NF-κB pathway inactivation. The evidence presented herein might provide a novel sight for asthma therapy.Copyright © 2020 Elsevier Ltd. All rights reserved.